Association between mediterranean diet and metal(loid) exposure in 4-5-year-old children living in Spain.

Even relatively low levels of metals exposure may impact health, particularly among vulnerable populations such as infants and young children. However, little is known about the interplay between simultaneous metal exposures, common in real-life scenarios, and their association with specific dietary patterns. In this study, we have evaluated the association between adherence to Mediterranean diet (MD) and urinary metal concentrations individually and as an exposure mixture in 713 children aged 4-5-years from the INMA cohort study. We used a validated food frequency questionnaire to calculate two MD indexes scores: aMED and rMED. These indexes gather information on various food groups within the MD and score differently. To measure urinary concentrations of cobalt, copper, zinc, molybdenum, selenium, lead, and cadmium as exposure biomarkers, we used inductively coupled plasma mass spectrometry (ICP-MS), coupled with an ion chromatography (IC) equipment for arsenic speciation analysis. We applied linear regression and quantile g-computation, adjusted for confounders, to analyse the association between MD adherence and exposure to the metal mixture. High adherence to MD such as the quintile (Q) 5 MD was associated with higher urinary arsenobetaine (AsB) levels than Q1, with ß values of 0.55 (confidence interval - CI 95% 0.01; 1.09) for aMED and 0.73 (CI 95% 0.13; 1.33) for rMED. Consumption of fish was associated with increased urinary AsB but reduced inorganic arsenic concentrations. In contrast, the aMED vegetables consumption increased urinary inorganic arsenic content. A moderate level of adherence to MD (Q2 and Q3) was associated with lower copper urinary concentrations than Q1, with ß values of -0.42 (CI 95% -0.72; -0.11) for Q2 and -0.33 (CI 95% -0.63; -0.02) for Q3, but only with aMED. Our study, conducted in Spain, revealed that adhering to the MD reduces exposure to certain metals while increasing exposure to others. Specifically, we observed increase in exposure to non-toxic AsB, highlighting the significance of consuming fish/seafood. However, it is crucial to emphasize the necessity for additional efforts in reducing early-life exposure to toxic metals, even when adhering to certain food components of the MD.

PFAS levels and exposure determinants in sensitive population groups.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants. The first exposure to PFAS occurs in utero, after birth it continues via breast milk, food intake, environment, and consumer products that contain these chemicals. Our aim was to identify determinants of PFAS concentrations in sensitive population subgroups- pregnant women and newborns. METHODS: Nine European birth cohorts provided exposure data on PFAS in pregnant women (INMA-Gipuzkoa, Sabadell, Valencia, ELFE and MoBa; total N = 5897) or newborns (3xG study, FLEHS 2, FLEHS 3 and PRENATAL; total N = 940). PFOS, PFOA, PFHxS and PFNA concentrations were measured in maternal or cord blood, depending on the cohort (FLEHS 2 measured only PFOS and PFOA). PFAS concentrations were analysed according to maternal characteristics (age, BMI, parity, previous breastfeeding, smoking, and food consumption during pregnancy) and parental educational level. The association between potential determinants and PFAS concentrations was evaluated using multiple linear regression models. RESULTS: We observed significant variations in PFAS concentrations among cohorts. Higher PFAS concentrations were associated with higher maternal age, primipara birth, and educational level, both for maternal blood and cord blood. Higher PFAS concentrations in maternal blood were associated with higher consumption of fish and seafood, meat, offal and eggs. In cord blood, higher PFHxS concentrations were associated with daily meat consumption and higher PFNA with offal consumption. Daily milk and dairy consumption were associated with lower concentrations of PFAS in both, pregnant women and newborns. CONCLUSION: High detection rates of the four most abundant PFAS demonstrate ubiquitous exposure of sensitive populations, which is of concern. This study identified several determinants of PFAS exposure in pregnant women and newborns, including dietary factors, and these findings can be used for proposing measures to reduce PFAS exposure, particularly from dietary sources.

Probabilistic Multiple-Bias Modeling Applied to the Canadian Data From the Interphone Study of Mobile Phone Use and Risk of Glioma, Meningioma, Acoustic Neuroma, and Parotid Gland Tumors.

We undertook a re-analysis of the Canadian data from the 13-country case-control Interphone Study (2001-2004), in which researchers evaluated the associations of mobile phone use with the risks of brain, acoustic neuroma, and parotid gland tumors. In the main publication of the multinational Interphone Study, investigators concluded that biases and errors prevented a causal interpretation. We applied a probabilistic multiple-bias model to address possible biases simultaneously, using validation data from billing records and nonparticipant questionnaires as information on recall error and selective participation. In our modeling, we sought to adjust for these sources of uncertainty and to facilitate interpretation. For glioma, when comparing those in the highest quartile of use (>558 lifetime hours) to those who were not regular users, the odds ratio was 2.0 (95% confidence interval: 1.2, 3.4). After adjustment for selection and recall biases, the odds ratio was 2.2 (95% limits: 1.3, 4.1). There was little evidence of an increase in the risk of meningioma, acoustic neuroma, or parotid gland tumors in relation to mobile phone use. Adjustments for selection and recall biases did not materially affect interpretation in our results from Canadian data.

Ultrafine particles and black carbon personal exposures in asthmatic and non-asthmatic children at school age.

Traffic-related air pollution (TRAP) exposure during childhood is associated with asthma; however, the contribution of the different TRAP pollutants in each microenvironment (home, school, transportation, others) in asthmatic and non-asthmatic children is unknown. Daily (24-h) personal black carbon (BC), ultrafine particle (UFP), and alveolar lung-deposited surface area (LDSA) individual exposure measurements were obtained from 100 children (29 past and 21 current asthmatics, 50 non-asthmatics) aged 9±0.7 years from the INMA-Sabadell cohort (Catalonia, Spain). Time spent in each microenvironment was derived by the geolocation provided by the smartphone and a new spatiotemporal map-matching algorithm. Asthmatics and non-asthmatics spent the same amount of time at home (60% and 61%, respectively), at school (20% and 23%), on transportation (8% and 7%), and in other microenvironments (7% and 5%). The highest concentrations of all TRAPs were attributed to transportation. No differences in TRAP concentrations were found overall or by type of microenvironment between asthmatics and non-asthmatics, nor when considering past and current asthmatics, separately. In conclusion, asthmatic and non-asthmatic children had a similar time-activity pattern and similar average exposures to BC, UFP, and LDSA concentrations. This suggests that interventions should be tailored to general population, rather than to subgroups defined by disease.

Mediterranean dietary pattern in pregnant women and offspring risk of overweight and abdominal obesity in early childhood: the INMA birth cohort study.

BACKGROUND: Animal models have suggested that maternal diet quality may reduce offspring obesity risk regardless of maternal body weight; however, evidence from human studies is scarce. OBJECTIVE: The aim of this study was to evaluate associations between adherence to the Mediterranean diet (MD) during pregnancy and childhood overweight and abdominal obesity risk at 4 years of age. METHODS: We analysed 1827 mother-child pairs from the Spanish 'Infancia y Medio Ambiente' cohort study, recruited between 2003 and 2008. Diet was assessed during pregnancy using a food frequency questionnaire and MD adherence by the relative Mediterranean diet score (rMED). Overweight (including obesity) was defined as an age-specific and sex-specific body mass index ≥85th percentile (World Health Organization referent), and abdominal obesity as a waist circumference (WC) >90th percentile. Multivariate adjusted linear and logistic regression models were used to evaluate associations between pregnancy rMED and offspring overweight and abdominal obesity. RESULT: There was no association between rMED and body mass index z-score, whereas there was a significant association between higher adherence to MD and lower WC (ß of high vs. low rMED: -0.62 cm; 95% confidence interval: -1.10, -0.14 cm, P for trend = 0.009). CONCLUSION: Pregnancy adherence to the MD was not associated with childhood overweight risk, but it was associated with lower WC, a marker of abdominal obesity.

Deficit of vitamin D in pregnancy and growth and overweight in the offspring.

BACKGROUND: Maternal vitamin D status during fetal development may influence offspring growth and risk of obesity; however, evidence in humans is limited. OBJECTIVE: To investigate whether maternal circulating 25-hydroxyvitamin D3 (25(OH)D3) concentration in pregnancy is associated with offspring prenatal and postnatal growth and overweight. METHODS: Plasma 25(OH)D3 concentration was measured in pregnant women (median weeks of gestation 14.0, range 13.0-15.0) from the INMA (INfancia y Medio Ambiente) cohort (Spain, 2003-2008) (n = 2358). Offspring femur length (FL), biparietal diameter (BPD), abdominal circumference (AC) and estimated fetal weight (EFW) were evaluated at 12, 20 and 34 weeks of gestation by ultrasound examinations. Fetal overweight was defined either as AC or as EFW ⩾ 90th percentile. Child's anthropometry was recorded at ages 1 and 4 years. Rapid growth was defined as a weight gain z-score of >0.67 from birth to ages 6 months and 1 year. Age- and sex-specific z-scores for body mass index (BMI) were calculated at ages 1 and 4 years (World Health Organization referent); infant's overweight was defined as a BMI z-score ⩾ 85th percentile. RESULTS: We found no association of maternal 25(OH)D3 concentration with FL and a weak inverse association with BPD at 34 weeks. Maternal deficit of 25(OH)D3 (<20 ng ml(-1)) was associated with increased risk of fetal overweight defined as AC ⩾ 90th percentile (odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.01-2.21; P = 0.041) or either as EFW ⩾ 90th percentile (OR = 1.47, 95% CI: 1.00-2.16; P = 0.046). No significant associations were found with rapid growth. Deficit of 25(OH)D3 in pregnancy was associated with an increased risk of overweight in offspring at age 1 year (OR = 1.42, 95% CI: 1.02-1.97; P = 0.039); however, the association was attenuated at age 4 years (OR = 1.19, 95% CI: 0.83-1.72; P = 0.341). CONCLUSIONS: Vitamin D deficiency in pregnancy may increase the risk of prenatal and early postnatal overweight in offspring. Clinical trials are warranted to determine the role of vitamin D in the early origins of obesity.

A conceptual framework in the study of neuropsychological development in epidemiological studies.

BACKGROUND: A wide range of neuropsychological development outcomes in children are currently measured in a large number of birth cohort and child cohort studies. METHODS: We summarized neuropsychological development assessment protocols from a number of birth cohort studies, reviews and specific books on child neuropsychology into a unifying conceptual framework. RESULTS: We suggest that neuropsychological development can be differentiated into two levels, i.e. functional and clinical. The functional level includes the skills, abilities, capacities and knowledge acquired during maturation of the brain as a result of the development of neural networks. It can be further divided into cognitive, psychomotor and social-emotional development subdomains. The clinical level includes the assessment of neurodevelopmental disorders or the presence of symptoms (subclinical symptomatology) of these disorders in populations under investigation in environmental epidemiology studies. CONCLUSIONS: Through explicit recognition of these levels of outcomes, and in using this framework, epidemiologists will be better able to design research through the informed selection of individual levels of outcomes. The framework also serves to standardize disparate terminologies across this field and allows for pooling of epidemiological data on neuropsychological endpoints where essentially similar levels of outcomes have been analyzed using different tests.

Estimation of RF energy absorbed in the brain from mobile phones in the Interphone Study.

OBJECTIVES: The objective of this study was to develop an estimate of a radio frequency (RF) dose as the amount of mobile phone RF energy absorbed at the location of a brain tumour, for use in the Interphone Epidemiological Study. METHODS: We systematically evaluated and quantified all the main parameters thought to influence the amount of specific RF energy absorbed in the brain from mobile telephone use. For this, we identified the likely important determinants of RF specific energy absorption rate during protocol and questionnaire design, we collected information from study subjects, network operators and laboratories involved in specific energy absorption rate measurements and we studied potential modifiers of phone output through the use of software-modified phones. Data collected were analysed to assess the relative importance of the different factors, leading to the development of an algorithm to evaluate the total cumulative specific RF energy (in joules per kilogram), or dose, absorbed at a particular location in the brain. This algorithm was applied to Interphone Study subjects in five countries. RESULTS: The main determinants of total cumulative specific RF energy from mobile phones were communication system and frequency band, location in the brain and amount and duration of mobile phone use. Though there was substantial agreement between categorisation of subjects by cumulative specific RF energy and cumulative call time, misclassification was non-negligible, particularly at higher frequency bands. Factors such as adaptive power control (except in Code Division Multiple Access networks), discontinuous transmission and conditions of phone use were found to have a relatively minor influence on total cumulative specific RF energy. CONCLUSIONS: While amount and duration of use are important determinants of RF dose in the brain, their impact can be substantially modified by communication system, frequency band and location in the brain. It is important to take these into account in analyses of risk of brain tumours from RF exposure from mobile phones.

Risk of brain tumours in relation to estimated RF dose from mobile phones: results from five Interphone countries.

OBJECTIVES: The objective of this study was to examine the associations of brain tumours with radio frequency (RF) fields from mobile phones. METHODS: Patients with brain tumour from the Australian, Canadian, French, Israeli and New Zealand components of the Interphone Study, whose tumours were localised by neuroradiologists, were analysed. Controls were matched on age, sex and region and allocated the 'tumour location' of their matched case. Analyses included 553 glioma and 676 meningioma cases and 1762 and 1911 controls, respectively. RF dose was estimated as total cumulative specific energy (TCSE; J/kg) absorbed at the tumour's estimated centre taking into account multiple RF exposure determinants. RESULTS: ORs with ever having been a regular mobile phone user were 0.93 (95% CI 0.73 to 1.18) for glioma and 0.80 (95% CI 0.66 to 0.96) for meningioma. ORs for glioma were below 1 in the first four quintiles of TCSE but above 1 in the highest quintile, 1.35 (95% CI 0.96 to 1.90). The OR increased with increasing TCSE 7+ years before diagnosis (p-trend 0.01; OR 1.91, 95% CI 1.05 to 3.47 in the highest quintile). A complementary analysis in which 44 glioma and 135 meningioma cases in the most exposed area of the brain were compared with gliomas and meningiomas located elsewhere in the brain showed increased ORs for tumours in the most exposed part of the brain in those with 10+ years of mobile phone use (OR 2.80, 95% CI 1.13 to 6.94 for glioma). Patterns for meningioma were similar, but ORs were lower, many below 1.0. CONCLUSIONS: There were suggestions of an increased risk of glioma in long-term mobile phone users with high RF exposure and of similar, but apparently much smaller, increases in meningioma risk. The uncertainty of these results requires that they be replicated before a causal interpretation can be made.

Ambient air pollution and risk of congenital anomalies in England, 1991-1999.

OBJECTIVES: To investigate whether there is an association between risk of congenital anomaly and annual ward level exposure to air pollution in England during the 1990s. METHODS: A geographical study was conducted across four regions of England using population-based congenital anomaly registers, 1991-1999. Exposure was measured as 1996 annual mean background sulphur dioxide (SO(2)), nitrogen dioxide (NO(2)) and particulate matter (PM(10)) concentrations at census ward level (n=1474). Poisson regression, controlling for maternal age, area socioeconomic deprivation and hospital catchment area, was used to estimate relative risk for an increase in pollution from the 10th to the 90th centile. RESULTS: For non-chromosomal anomalies combined, relative risks were 0.99 (95% CI 0.93 to 1.05) for SO(2), 0.97 (95% CI 0.84 to 1.11) for NO(2) and 0.89 (95% CI 0.75 to 1.07) for PM(10). For chromosomal anomalies, relative risks were 1.06 (95% CI 0.98 to 1.15) for SO(2), 1.11 (95% CI 0.95 to 1.30) for NO(2) and 1.18 (95% CI 0.97 to 1.42) for PM(10). Raised risks were found for tetralogy of Fallot and SO(2) (RR=1.38, 95% CI 1.07 to 1.79), NO(2) (RR=1.44, 95% CI 0.71 to 2.93) and PM(10) (RR=1.48, 95% CI 0.57 to 3.84), which is of interest in light of previously reported associations between this cardiac anomaly and other air pollutants. CONCLUSIONS: While air pollution in the 1990s did not lead to sustained geographical differences in the overall congenital anomaly rate in England, further research regarding specific anomalies is indicated.

Determinants of mobile phone output power in a multinational study: implications for exposure assessment.

OBJECTIVES: The output power of a mobile phone is directly related to its radiofrequency (RF) electromagnetic field strength, and may theoretically vary substantially in different networks and phone use circumstances due to power control technologies. To improve indices of RF exposure for epidemiological studies, we assessed determinants of mobile phone output power in a multinational study. METHODS: More than 500 volunteers in 12 countries used Global System for Mobile communications software-modified phones (GSM SMPs) for approximately 1 month each. The SMPs recorded date, time, and duration of each call, and the frequency band and output power at fixed sampling intervals throughout each call. Questionnaires provided information on the typical circumstances of an individual's phone use. Linear regression models were used to analyse the influence of possible explanatory variables on the average output power and the percentage call time at maximum power for each call. RESULTS: Measurements of over 60,000 phone calls showed that the average output power was approximately 50% of the maximum, and that output power varied by a factor of up to 2 to 3 between study centres and network operators. Maximum power was used during a considerable proportion of call time (39% on average). Output power decreased with increasing call duration, but showed little variation in relation to reported frequency of use while in a moving vehicle or inside buildings. Higher output powers for rural compared with urban use of the SMP were observed principally in Sweden where the study covered very sparsely populated areas. CONCLUSIONS: Average power levels are substantially higher than the minimum levels theoretically achievable in GSM networks. Exposure indices could be improved by accounting for average power levels of different telecommunications systems. There appears to be little value in gathering information on circumstances of phone use other than use in very sparsely populated regions.

Mortality from diseases other than cancer following low doses of ionizing radiation: results from the 15-Country Study of nuclear industry workers.

BACKGROUND: Ionizing radiation at very high (radio-therapeutic) dose levels can cause diseases other than cancer, particularly heart diseases. There is increasing evidence that doses of the order of a few sievert (Sv) may also increase the risk of non-cancer diseases. It is not known, however, whether such effects also occur following the lower doses and dose rates of public health concern. METHODS: We used data from an international (15-country) nuclear workers cohort study to evaluate whether mortality from diseases other than cancer is related to low doses of external ionizing radiation. Analyses included 275 312 workers with adequate information on socioeconomic status, over 4 million person-years of follow-up and an average cumulative radiation dose of 20.7 mSv; 11 255 workers had died of non-cancer diseases. RESULTS: The excess relative risk (ERR) per Sv was 0.24 [95% CI (confidence intervals) -0.23, 0.78] for mortality from all non-cancer diseases and 0.09 (95% CI -0.43, 0.70) for circulatory diseases. Higher risk estimates were observed for mortality from respiratory and digestive diseases, but confidence intervals included zero. Increased risks were observed among the younger workers (attained age <50 years, identified post hoc) for all groupings of non-cancer causes of death, including external causes. It is unclear therefore whether these findings reflect real effects of radiation, random variation or residual confounding. CONCLUSIONS: The most informative low-dose radiation study to date provides little evidence for a relationship between mortality from non-malignant diseases and radiation dose. However, we cannot rule out risks per unit dose of the same order of magnitude as found in studies at higher doses.

The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: estimates of radiation-related cancer risks.

A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.

The 15-Country Collaborative Study of Cancer Risk Among Radiation Workers in the Nuclear Industry: design, epidemiological methods and descriptive results.

Radiation protection standards are based mainly on risk estimates from studies of atomic bomb survivors in Japan. The validity of extrapolations from the relatively high-dose acute exposures in this population to the low-dose, protracted or fractionated environmental and occupational exposures of primary public health concern has long been the subject of controversy. A collaborative retrospective cohort study was conducted to provide direct estimates of cancer risk after low-dose protracted exposures. The study included nearly 600,000 workers employed in 154 facilities in 15 countries. This paper describes the design, methods and results of descriptive analyses of the study. The main analyses included 407,391 nuclear industry workers employed for at least 1 year in a participating facility who were monitored individually for external radiation exposure and whose doses resulted predominantly from exposure to higher-energy photon radiation. The total duration of follow-up was 5,192,710 person-years. There were 24,158 deaths from all causes, including 6,734 deaths from cancer. The total collective dose was 7,892 Sv. The overall average cumulative recorded dose was 19.4 mSv. A strong healthy worker effect was observed in most countries. This study provides the largest body of direct evidence to date on the effects of low-dose protracted exposures to external photon radiation.

Validation of short term recall of mobile phone use for the Interphone study.

AIM: To validate short term recall of mobile phone use within Interphone, an international collaborative case control study of tumours of the brain, acoustic nerve, and salivary glands related to mobile telephone use. METHODS: Mobile phone use of 672 volunteers in 11 countries was recorded by operators or through the use of software modified phones, and compared to use recalled six months later using the Interphone study questionnaire. Agreement between recalled and actual phone use was analysed using both categorical and continuous measures of number and duration of phone calls. RESULTS: Correlations between recalled and actual phone use were moderate to high (ranging from 0.5 to 0.8 across countries) and of the same order for number and duration of calls. The kappa statistic demonstrated fair to moderate agreement for both number and duration of calls (weighted kappa ranging from 0.20 to 0.60 across countries). On average, subjects underestimated the number of calls per month (geometric mean ratio of recalled to actual = 0.92, 95% CI 0.85 to 0.99), whereas duration of calls was overestimated (geometric mean ratio = 1.42, 95% CI 1.29 to 1.56). The ratio of recalled to actual use increased with level of use, showing underestimation in light users and overestimation in heavy users. There was substantial heterogeneity in this ratio between countries. Inter-individual variation was also large, and increased with level of use. CONCLUSIONS: Volunteer subjects recalled their recent phone use with moderate systematic error and substantial random error. This large random error can be expected to reduce the power of the Interphone study to detect an increase in risk of brain, acoustic nerve, and parotid gland tumours with increasing mobile phone use, if one exists.

Prevalence of congenital anomalies in five British regions, 1991-99.

AIMS: To describe trends in total and live birth prevalence, regional differences in prevalence, and outcome of pregnancy of selected congenital anomalies. METHODS: Population based registry study of 839,521 births to mothers resident in five geographical areas of Britain during 1991-99. Main outcome measures were: total and live birth prevalence; pregnancy outcome; proportion of stillbirths due to congenital anomalies; and secular trends. RESULTS: The sample consisted of 10,844 congenital anomalies, giving a total prevalence of 129 per 10,000 registered births (95% CI 127 to 132). Live birth prevalence was 82.2 per 10,000 births (95% CI 80.3 to 84.2) and declined significantly with time. The proportion of all stillbirths with a congenital anomaly was 10.5% (453 stillbirths). The proportion of pregnancies resulting in a termination increased from 27% (289 cases) in 1991 to 34.7% (384 cases) in 1999, whereas the proportion of live births declined from 68.2% (730 cases) to 58.5% (648 cases). Although similar rates of congenital anomaly groups were notified to the registers, variation in rates by register was present. There was a secular decline in the total prevalence of non-chromosomal and an increase in chromosomal anomalies. CONCLUSIONS: Regional variation exists in the prevalence of specific congenital anomalies. For some anomalies this can be partially explained by ascertainment variation. For others (neural tube defects, diaphragmatic hernia, gastroschisis), higher prevalence rates in the northern regions (Glasgow and Northern) were true differences. Live birth prevalence declined over the study due to an increase in terminations of pregnancy.

Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.

OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Congenital anomaly surveillance in England--ascertainment deficiencies in the national system.

OBJECTIVE: Firstly, to assess the completeness of ascertainment in the National Congenital Anomaly System (NCAS), the basis for congenital anomaly surveillance in England and Wales, and its variation by defect, geographical area, and socioeconomic deprivation. Secondly, to assess the impact of the lack of data on pregnancies terminated because of fetal anomaly. DESIGN: Comparison of the NCAS with four local congenital anomaly registers in England. SETTING: Four regions in England covering some 109,000 annual births. PARTICIPANTS: Cases of congenital anomalies registered in the NCAS (live births and stillbirths) and independently registered in the four local registers (live births, stillbirths, fetal losses from 20 weeks' gestation, and pregnancies terminated after prenatal diagnosis of fetal anomaly). MAIN OUTCOME MEASURE: The ratio of cases identified by the national register to those in local registry files, calculated for different specified anomalies, for whole registry areas, and for hospital catchment areas within registry boundaries. RESULTS: Ascertainment by the NCAS (compared with data from local registers, from which terminations of pregnancy were removed) was 40% (34% for chromosomal anomalies and 42% for non-chromosomal anomalies) and varied markedly by defect, by local register, and by hospital catchment area, but not by area deprivation. When terminations of pregnancy were included in the register data, ascertainment by NCAS was 27% (19% for chromosomal anomalies and 31% for non-chromosomal anomalies), and the geographical variation was of a similar magnitude. CONCLUSION: The surveillance of congenital anomalies in England is currently inadequate because ascertainment to the national register is low and non-uniform and because no data exist on termination of pregnancy resulting from prenatal diagnosis of fetal anomaly.

Risk of congenital anomalies near the Byker waste combustion plant.

BACKGROUND: The aim of this study was to determine whether the risk of congenital anomalies in a population resident close to a waste combustion plant located at Byker in the city of Newcastle upon Tyne, United Kingdom, was higher than in a population resident further away. METHODS: A geographical study was carried out on the prevalence of congenital anomalies in residents living within 3 km (inner zone) of the Byker combustion plant compared with those living 3-7 km (outer zone) from the plant. There were 81255 live births (1985-1999) and 1508 cases with chromosomal and non-chromosomal congenital anomalies. The cases were identified from the Northern Region Congenital Abnormality Survey. RESULTS: After the site commenced operation the estimated rate ratio (inner versus outer zone) was 1.11 (95 per cent confidence interval (CI) 0.96-1.28) adjusted for socio-economic deprivation. There was significant heterogeneity across years and an increasing trend, of marginal significance (p = 0.07), in the rate ratio. The inner zone rate approached or became significantly higher than that in the outer zone in some of the later years. CONCLUSIONS: No significant overall association between the number of congenital anomalies and proximity of residence to the Byker waste combustion plant has been found in this study. Significantly increased rates near the site during the later years may suggest a possible risk but are difficult to interpret. More comprehensive, multi-site investigations around other waste combustion plants are indicated.

Risk of hypospadias in relation to maternal occupational exposure to potential endocrine disrupting chemicals.

BACKGROUND: Reported rises in the prevalence of hypospadias and other abnormalities of the male reproductive system may be a result of exposure to endocrine disrupting chemicals. AIMS: To analyse the relation between risk of hypospadias and maternal occupation, particularly with regard to exposure to potential endocrine disrupting chemicals (EDCs). METHODS: Data (1980-96) from the National Congenital Anomaly System (NCAS) were used to analyse the proportion of all congenital anomaly cases (n = 35 962) which were notified with hypospadias (n = 3471) by occupational codes (348 individual job titles) and by categories of exposure to potential EDCs from a job exposure matrix. RESULTS: Five individual occupations (of 348) showed nominally statistically significant excesses, none of which had possible or probable exposure to potential EDCs. Odds ratios for "possible" or "probable" compared to "unlikely" exposure to potential EDCs did not show statistically significant increases in any of the EDC categories after adjustment for social class of the mother and father, nor was there evidence of an upward trend in risk with likelihood of exposure. In the 1992-96 time period odds ratios were increased for hairdressers (the largest group exposed to potential EDCs) and for probable exposure to phthalates (of which hairdressers form the largest group) before social class adjustment. CONCLUSIONS: There was little evidence for a relation between risk of hypospadias and maternal occupation or occupational exposure to potential EDCs, but as the exposure classification was necessarily crude, these findings should be interpreted with caution.